VITAMIN C and ALLERGY TREATMENT
Submitted to Medical Hypotheses February 1986
作者:Robert F. Cathcart, M.D.
来源:www.orthomed.com
翻译:蓝山
过敏的维生素C治疗和抗体的正常非激活状态
A摘要：
我以前叙述病人对口服维生素C（即抗坏血酸，AA）的肠耐受极限（几乎引起腹泻）某种程度上随其疾病的毒性的增加而增加。在接近肠耐受极限的非常高的阈限水平，高浓度的维生素C，使氧化还原配对---抗坏血酸/脱氢抗坏血酸（AA/DHA）的氧化还原电位，在病变组织变为还原状态。维生素C改善症状，有时甚至治愈某些疾病。过敏和过敏反应通常都会改善，有时被完全阻断。我现在推测，大剂量的维生素C阻断过敏反应的其中一个机制是抗体分子中的二硫键的还原，使抗体和抗原的结合成为不可能。我进一步推测：抗体只在有大量游离的自由基或相对氧化态的氧化还原电位的组织和抗原结合。正常健康组织的氧化还原状态不允许抗体和抗原结合。当抗氧化剂、自由基清除系统被控制，炎症的、过敏的和“自身免疫”病况就会发生。
介绍
依照过去15年我治疗超过15000病人的临床经验，我的连续观察的结果是，一个耐受维生素C的病人，把维生素C溶于水中口服不引起腹泻的量，大概随其疾病的毒性的增加而增加。一个正常时24小时分多次口服10~15克维生素C的人，如患一般感冒，可耐受30~60克；如患严重感冒，可耐受100克；如患流感，可耐受150克；如患单核细胞增多症和病毒性肺炎，可耐受200克。有枯草热、哮喘或咳嗽、药物和食物过敏和敏感的病人，通常24小时内耐受10~50克维生素C，分成4~12次口服。偶然情况下，耐受量可提高至更高水平。病人的症状通常在腹泻出现以前出现意想不到的减轻。 要达到这种效果，病人一定要耐受口服维生素C，但至少80%的人可耐受足够的量。我称这种由病人自己测定合适的维生素C剂量的过程为滴定至肠耐受极限。静脉注射维生素C钠甚至更有效。
我曾推测，这种改善效果是由于维生素C的抗氧化剂、自由基清除效应。另外，我曾推测，在病变过程中形成的氧化物和自由基，开始在病变涉及组织，然后在整个身体，依次消耗维生素C。然后，开始在病变组织，之后在全身不再有维生素C的存在，以维持所知的维生素C功能。 我称这种现象为“急性诱发性坏血病”。我认为这种机制适用于过敏和过敏反应中形成的自由基的任何程度。我有许多临床证据表明大量抗坏血酸会改善外伤和外科手术后继发的炎症性串联反应。
我曾推测，大量抗坏血酸突然变得有效的阈限是在抗坏血酸/脱氢抗坏血氧化还原配对在受感染组织变成还原戊的氧化还原配对（5）。抗坏血酸在还原自由基和正在氧化的物质中形成的脱氢抗坏血酸，其毒性比其还原的物质小，脱氢抗坏血酸的氧化还原电位比其氧化的自由基和氧化性物质少。此外，如果吸入的抗坏血酸足够令抗坏血酸/脱氢抗坏血酸氧化还原配对在受感染组织变为还原态物质，形成的脱氢抗坏血酸将没有任何毒性。我们不应该只认为抗坏血酸为一种还原性物质而脱氢抗坏血酸为一种氧化性物质，而应该联想到这种氧化还原配对AA/DHA的氧化还原电位。我可以忽视已形成的DHA的任何氧化作用，只要确保，病人经常服用或注射足够的抗坏血酸，令抗坏血酸以高于脱氢抗坏血酸的浓度进入病变组织的内部。病变组织的内部的氧化还原配对AA/DHA的氧化还原电位变为还原性质。
抗坏血酸阻断过敏反应
我已发现抗坏血酸在肠耐受极限量水平可阻断许多过敏反应。当我少量接触花粉后出现的枯草热症状可用24小时分次服用抗坏血酸而控制，我就注意到这种可能性了。然而，若接触更多的花粉，需要增加抗坏血酸量以维持适度的症状阻断。急性接触抗原可增加肠耐受量至每24小时50克或更多。若接触的抗原太多，症状的阻断通常是不完全的。至少1000例过敏病人的验证显示，绝大多数病人都已证实了这个发现。限制性因素常常看来是病人持续口服几乎引起腹泻的抗坏血酸的适应能力。抗坏血酸治疗和其他治疗相结合甚至可产生更优化的效果。
哮喘发作亦常常被类似改善。当哮喘由运动诱发，运动前后和运动过程中服用大量抗坏血酸常常可阻止其他情况下预期会出现的哮喘发作。由感染、尤其是上呼吸道感染激发的哮喘，最易被抗坏血酸预防。抗坏血酸在这些病例中的有效程度大多数取决于病人能否服用足够量的抗坏血酸。在急性、严重的情况下，对那些不能口服足够抗坏血酸量的病人，静脉注射抗坏血酸可能尤其有效。
荨麻疹、蜜蜂叮、毒橡胶、湿疹等，取决于病人耐受抗坏血酸的程度和其他未查明的变数，亦有不同程度的改善。对这些过敏病变，抗坏血酸和其他治疗起协同作用。
猩红热
有典型的沙纸样皮疹的三个猩红热病人接受抗坏血酸治疗。病人的皮疹、发热和其他症状在口服肠耐受极限量的抗坏血酸的几个小时内消失。抗坏血酸在猩红热发烧和一些食物中毒的效果是如此扣人心弦，以至认为是对一种在疾病过程中不能被再补充的有限量的毒性物的破坏。
药物反应
大约2000例病人用青霉素、安苄青霉素和先锋霉素，配合肠耐受极限量的抗坏血酸，没有产生任何即时过敏反应。有一少年有对青霉素的延迟型血清病样反应。她的症状用大量抗坏血酸短时间内减轻。最可能是她没有服用足够量的抗坏血酸，以获得阻断过敏反应的效果。
几个单核细胞增多症病人偶然地给予青霉素连同抗坏血酸一起服用，没有任何过敏反应。这种经历是鲜明的，因为单核细胞增多症的病人对青霉素有很高的过敏反应发生率。一个给予青霉素治疗而无服用抗坏血酸的病人出现典型的过敏反应皮疹，给予静脉注射抗坏血酸后，令皮疹在数分钟消失。
由于抗坏血酸预防几种抗生素的过敏反应变得越来越明显，我扩大了其对多种抗生素的保护范围。虽然顽固的念株菌感染的治疗是复杂的，且只有结合其他治疗才能生效，很容易因接受抗生素治疗而出现阴道霉菌感染的妇女，当服用抗坏血酸至肠耐受极限量配合抗生素治疗，有明显的并发症减轻。另外，抗坏血酸看来和抗生素有协同作用，并明显增大抗生素的抗菌谱。
目前为止，在服用大剂量抗坏血酸时，我未有一个病人发生对任何药物的过敏反应。过敏反应的可能性是如此之少，令这种观察价值有限。然而，抗坏血酸改善病状的范围，提示只要有任何一点过敏反应的危险，抗坏血酸都应作为治疗的一部分，和其他治疗一同使用。
Kalokerinos (6)的观察，抗坏血酸预防婴儿突发死亡综合征，可能是或不是和这有关，只要有任何可能，同类实验值得重复。
抗坏血酸不是严格意义上的抗组胺药
虽然抗坏血酸有抗组织胺样作用，它不是严格意义上的抗组胺药。许多抗组胺药有乙胺部分，正如在组织胺中的，但抗坏血酸没有。抗组胺药看来通过占据效应细胞的受体位置并排斥组织胺而发挥作用。它们是药理拮抗药，抗坏血酸对中枢神经系统没有任何兴奋作用，正如大部分抗组织胺药一样。通过抗坏血酸改善大脑和身体的不适以及某些毒性反应，可能会被病人理解为有些中枢兴奋作用。当然，抗坏血酸和抗组织胺药不同，对中枢神经系统没有任何抑制作用。抗坏血酸没有任何局部麻醉作用以及在某些抗组胺药发现的萎缩作用。抗坏血酸对中枢神经系统没有任何急性毒性反应，不管其剂量如何，而抗组胺药则有。
Lewin阐述抗坏血酸的机制是其帮助C-AMP（9）的形成，而C-AMP抑制组织胺从肥大细胞或嗜碱性粒细胞的释放。但这不是抗组织胺的效果。
因此，抗坏血酸在某些病例中，可能会发现有类似抗组织胺有益的临床效果。但抗坏血酸通常可以改善抗组胺药不能改善的病变。另外，抗坏血酸看来和抗组胺药发挥协同作用。抗组胺药当然不认为是抗组胺药，没有任何类似的抗组胺作用。
食物过敏、敏感和中毒
食物过敏，正如那些产生免疫球蛋白IgE调节的症状如荨麻疹样皮疹，对抗坏血酸反应很快。服用抗坏血酸至肠耐受极限量水平，直至产生稀软性大便、甚至腹泻，减少胃肠排空时间。除了阻断反应外，尚缩短反应的时间。
不能由IgE调节的食物敏感或反应，通常表现为更为难治，但应该尝试肠耐受极限量方法。取决于其内在原因，你可预期相当部分病人的反应强度会减轻，反应的持续时间缩短。
食物中毒和急性肠胃炎可用大量抗坏血酸被意想不到的改善。治疗这些病变，经验是有帮助的，因为病人会担心抗坏血酸会加重其腹泻和其他肠胃不适。如果是健康肠胃，比正常的耐受量大的抗坏血酸配给病人，将无任何困难。这些剂量通常不会增加腹泻，而是减少腹泻。如果偶然大大过量，腹泻将会产生，但所有其他毒性症状都有会减轻。同时腹泻是良性的，通常不会疼痛。
虽然不是经常成功，我经常测试抗坏血酸对食物和化学物过敏病人的效果。肠耐受极限量的抗坏血酸常有缓解作用。由于常见的令人讨厌的原因，这些病人通常难以服用足够的量。大量气体的产生是常见的。有这种过敏的许多病人有肠道菌群（含白色念株菌）和其他产气微生物。气体的大量产生常提示念株菌和微生物实际上正在发酵抗坏血酸，或者抗坏血酸轻微加速他们发酵其他食物。然而，一些病人看来突破一个障碍，即使大量的抗坏血酸亦减少气体的产生的数量。也许，大量抗坏血酸导致的通过肠道的时间的减少实际上排泄很多产气菌群，或者，抗坏血酸的足够高水平最终抑扬制发酵。有趣地，在病人尽量口服大量抗坏血酸的同时，每日60克，坚持1日或2日的大量抗坏血酸钠静脉注射，能以这样一种方式“激活”病人，耐受口服大量的抗坏血酸。饥饿和杀灭肠道念株菌的措施应加以采取，有效时，会减少肠道产气。
这些病人的一部分会对抗坏血酸的原料产生过敏。我发现，改用由玉米浆制造的合成抗坏血酸精粉，这些过敏反应的发生率下降了。经验表明，有时将会出现，不是抗坏血酸本身引起过敏反应，而是制造过程中的微量污染物导致过敏反应。如果服用一种抗坏血酸出现问题，应试用另一种形式的抗坏血酸，由sego palm（一种棕榈）制造的抗坏血酸，一些原料标称“天然”，有时片剂，或者是缓释剂型，也会被病人更好地耐受。但这些剂型更昂贵，同时，如初次使用可能更易导致过敏反应。用替代形式的抗坏血酸的最严重问题是它们可能没有相同的效果，因为其达到的抗坏血酸水平通常不如前者高
如果矿物抗坏血酸被使用，应注意的事实是，这里讨论的是抗坏血酸部分，而服用的矿物质的数量应作考虑。矿物抗坏血酸从多种方式影响肠耐受极限量。钙、镁和钾盐有时被过敏病人用于阻断过敏反应，以及，当病人有效时，可能以抗坏血酸盐形式使用，这介绍了一个超出本篇范畴的话题。
虽然不是经常成功，使每个食物过敏病人尝试肠耐受极限量是值得的。如果肠耐受，肠耐受极限量可以不同程度缓解食物和化学物过敏症状。
抗坏血酸对IgE和其他免疫球蛋白调节的过敏反应的明确效果已给我启示：可用特别的生物化学术语理解的一个可能的作用模式。
抗体的结构
虽然有五类明显的免疫球蛋白：IgG、IgA、IgD、IgE、IgM 抗体，免疫球蛋白结构的基本单位是由2 条相同的轻多肽链和2条相同的重多肽链通过二硫键（SS）连结在一起。这个基本单位的典型模式是使这些肽链排列为一个“Y”字形。2条重链形成一夹角，指向它们的中间，并被二硫键连在一起，以这样一种形式排列在一起，以形成Y“字的底部。这个底部，或Fc段，调节抗体对机体组织，包括免疫系统的各种细胞、一些巨噬细胞和补体的结合。连结在“Y”底部的双硫键在不同的抗体纲，甚至不同的亚纲的免疫球蛋白，各不相同。以IgE为例，5个基本单位在它们的底部连结起来。
2条轻肽链的其中一条连结到“Y”字形状的重肽链的其中一条“V”,通过一个二硫键连结在一起，命名为：Fab段。Fab段的上端是专一抗原结合点--抗原被捆绑的位置。
虽然下列比喻涉及某些不准确之处，想象“V”字的每条残基为衣服别针，两条木制部分被一条弹簧连在一起。弹簧代表二硫键。木质部分的远端叫可变区，同时，可变形以适合不同的抗原。当抗体的那对“服装别针”发现一个抗原配对，它们和抗原结合。
在IgE分子中，有20个二硫键，16个是链内键，2个是链间键，在Fc段的上部的夹角附近连接2条重链。1条链间二硫键在夹角附近连接一整条轻链和邻近的重链。在动物实验中，通过连续增加还原剂如二硫苏糖醇（DTT）的浓度和烷基化，任何人均可裂解二硫键（14）。用1mM的DTT浓度，重链和轻链间的二硫键被裂解。这些键是位于结合抗原的可变区，类似从衣服别针取出弹簧一样，抗体变得不能和抗原结合。在一个2mM的DTT浓度，位于夹角附近的重链的二硫键被还原，攻击细胞的能力显著下降，如是IgE，是嗜碱细胞和肥大细胞。更高浓度的DTT将导致更多的还原，以及IgE的断裂。
Lewin (9)用生物化学方法分析了抗坏血酸在体内帮助二硫键还原的复杂情况：他推论：在体内环境下，当抗坏血酸供应充足时，抗坏血酸/脱氢抗坏血酸系统可以还原硫氢基/二硫化合物系统（如抗坏血酸能还原二硫键）。虽然Lewin 没有专门提到抗体的二硫键，他确提到DTT、胱氨酸、谷胱甘肽和肾上腺色素等等。
以符号表示，反应可表示为：
AA=DHA+2e+2H+
-S-S-+2H+2=2-SH
从Lewin 对体内多个代谢系统的分析，任何人均可获得如下印象：一些系统很可能是处于抗坏血酸/脱氢抗坏血酸的等式中，如果AA/DHA比值高，系统将会被还原，并带来有益的影响。我的临床经验已验证了这些印象。我和Lewin 不同之处仅是，在临床严重情况下，取得这些效果需要的抗坏血酸剂量是他预期的10~15倍。
抗体的解离
临床上，过敏反应被抗坏血酸阻断的程度大约和抗坏血酸被挤入受感染组织的阈限浓度直接相关。抗坏血酸需要的量，看来和受感染组织的炎症程度成正比。起效的抗坏血酸的阈限量，应该可足够还原自由基和在感染组织形成的其他氧化物。在这些组织一个相对还原的氧化还原电位，还原抗原和抗体末端结合的二硫键。
我推测，正常水平的抗坏血酸和其他抗氧化剂的一个重要作用是还原任何抗体的二个抗原结合端的每一个链间二硫键。抗原结合终端被改变成这样一种形式，以致它们不能结合任何物质。这些小片不会每个方向散去，而可能结合在一起，可能是范得华力的结果，但仍不能结合任何物质。
另外，我推测这“未激活”状态是正常健康组织的抗体的正常状态。除非抗体游进充满自由基或相对氧化的氧化还原状态的组织，抗体不会被激活以和抗原结合。在人类的问题是，由于外科手术、外伤、感染、过敏反应等等，感染组织的氧化还原状态，因为自由基和氧化物以及自身不能合成抗坏血酸，很容易变为更少的还原状态，在不必要的广泛组织，抗体被激活并持续太长的时间。
最初，这种未激活效应在某些情况下似乎非常不理想，但我认为，抗坏血酸帮助身体调节至最优化水平。并且，抗体对枯草热、哮喘和荨麻疹等的反应无任何益处，而抗坏血酸阻断这些反应是理想的。一个理想的情形将是，花粉无害粘在粘膜上，不会被抗体结合，因为抗体未被激活，但，如果细菌或病毒等，释放毒素去避开免疫系统，应激活抗体，并促使抗体寻找并和抗原结合。
在我接触自身能合成抗坏血酸的动物的有限经验中，我已注意到，在外科手术、外伤和感染的情况下，动物比人看来有更短的疼痛期和功能丧失期，似乎动物没有人类常见的继发炎症连串反应的程度。这种现象亦被兽医们所证实。我在滑雪地区处理许多受伤的病人时的经验，虽然，外伤或外科手术后的急性疼痛不能减轻，如果使身体充满抗坏血酸，次日疼痛显著减轻。若外伤完全固定或不受干扰，24小时内无任何疼痛是常见的。同时，没有继发炎症是非常显著的。
我处理撕脱碎片的经验是，当皮片正确地再植，亦就是当再植时，皮肤碎片尚可用的，它几乎肯定能生存。当服用大剂量抗坏血酸时，由继发炎症导致的循环损伤而产生的自体移植坏死基本上消失了。
在感染情况下，服用抗坏血酸至肠耐受极限量的病人，炎症程度和持续时间看来均减少。炎症看来更局限于受感染的局部。然而，大多数被抗坏血酸缩短或消除的炎症，看来被与炎症无关的机制所引起。许多感染治疗中，减轻炎症的理论价值如何，可通过许多医生在治疗感染时，有时使用类固醇来验证。尽管事实上，类固醇看来抑制一些感染对抗机制。相反，足量的抗坏血酸看来阻断炎症至更优化的程度，同时，增强各种炎症对抗机制。
我认为，抗坏血酸，在此刻讨论的水平，设法还原除自由基高度集中的直接受到感染的病灶外的抗体链间的二硫键。在感染组织的内部，抗坏血酸在保护邻近组织免受自由基损害的同时，帮助吞噬细胞维持其吞噬功能。
继发串联炎症反应被清除自由基的大剂量抗坏血酸切断。因此，防止大面积不必要的相对氧化的氧化还原电位的形成。抗体因此保持未激活状态，除了在被外伤、或感染严重、直接影响的小数病灶外，抗体被阻止和抗原不必要地结合，否则，其他情况下，必会出现大面积的继发炎症。因此，演变为自身免疫反应的可能性被大大减低了。
我的推测绝对不是忽视已经创立的，以解释免疫应答的必要控制的高贵的免疫调节机制，但它增加了一个十分有效的控制机制，以显著限制更复杂的病理机制肯定起作用的病灶范围。
自身免疫反应
临床上，当一个病人继发其他病变的时候，抱怨旧伤或旧感染复发并非少见。由轻度改变的自身分子形成的抗体，被旧伤或旧感染轻度改变，由于原始的炎症消退在最初侵害时被抑制。抗体反应得到控制的多种免疫调节机制已被阐述（15）。我推想另外一种抑制免疫反应的机制是随着组织相对还原的氧化还原电位的恢复，抗体变为还原态和“未激活”状态。当病人的自由基清除系统被这些病变克制，体内多个系统的氧化还原电位变得更趋氧化态，因而，旧的抗体开始寻求配对。一些以前受伤时形成的抗体可能会和以前受感染的组织配对，导致疼痛和炎症。此外，那些抗体可和以前受感染的组织相类似的组织发生交叉反应。导致更广泛的病变如关节炎、肌炎、腱炎、神经炎等均可能发生。异体分子，尤其是食物和化学物，类似地会增加和自身分子发生交叉反应。抗坏血酸在避免这种结果的出现有极好的效果，因为系统的氧化还原电位保持相对还原状态，虽然局部病理过程产生相当数量的自由基。
有些时候，顽固的自身免疫反应可通过大剂量的抗坏血酸驱使还原态的氧化还原电位直接进入自身免疫反应的内部而明显减轻。常常是，如果高水平的抗坏血酸被维持，使大多数自身免疫反应，但并非全部，被阻断，变态反应可变为间歇性的，而显示病变和以前未被怀疑的抗原有关，并且并非是一个真正的自身免疫反应。在怀疑有食物和化学物过敏的病人，可能很难通过病史确定那种食物和化学物引起过敏反应，因为反应持续多天。通常，这些过敏反应的持续时间，可用大剂量抗坏血酸缩短，过敏反应的原因变得更加清楚。
可变性过敏
病人对是否对某些物质过敏产生迷惑并非不常见，因为有时，他对其有反应，有时却没有。如果，如病人有对一些牛奶蛋白过敏的抗体，但此时他不受任何压力，没有任何炎症，自由基清除系统在所有组织维持一个相对还原的氧化还原电位，那么，病人将可以喝一些牛奶，因为所有抗体都处于一种“未激活”状态。但，如果全身或接触牛奶的消化道局部的自由基清除系统已被控制，抗体将会被激活，并将会发生反应，如果接触牛奶的话。
自由基清除剂可被系统地耗竭，可由接触化学物如：甲醛；慢性感染如EB（Epstein-Barr）病毒感染，其他过敏反应、外伤、情绪紧张等，导致抗体系统性激活，越多抗体系统性激活，越大可能发生抗体和自身分子的交叉反应，以及自身免疫反应出现。
局部反应可消除部分自由基清除剂和激活抗体。这种形式中特别麻烦的是念株菌，可激活消化道抗体，导致对念株菌发生过敏反应。阿米巴，肠贾第虫，和其他胃肠道病原体可类似作用。随着炎症反应变得剧烈和更多自由基被释放，广泛组织产生更趋氧化态的氧化还原电位，更多抗体被激活，其敏感性变得更严重、更多数量。肿胀的粘膜不能合成合适的消化酶。因此更多大分子（如未消化的全食物蛋白）会进入机体，更可能引起配对抗体的产生。
有关的变数
患病的粘膜和皮肤更易让各种抗原，包括未被恰当消化的大分子进入体内。饮食不当或由于压力导致某些营养素的过度利用，导致缺乏制造这些酶的营养素，可发生消化酶缺乏症。饮食不当或压力亦可导致自由基清除剂不足，以保持足够还原态的氧化还原电位使抗体不被激活。罐头食品可令病人对正常的食品过敏。我曾看过食糖摄入诱发对花粉过敏的枯草热发作。
另一方面，对接触抗原的解脱使身体减缓炎症反应，暂时维持自由基清除作用，以及，因为抗体未激活，使身体暂时耐受抗原。比如，一个易患枯草热的病人，置身于一个完全无花粉的环境一段时间后，因为其鼻子的抗体变成未激活状态，可耐受轻度的花粉而不会立即发生过敏反应。由于局部剌激开始于鼻粘膜，一种更加氧化态的氧化还原电位在局部形成，抗体在广泛组织激活，一个更严重的过敏反应接着出现。大剂量的抗坏血酸使局部保持更大程度的还原状态，使身体耐受更大浓度的花粉，取决于抗坏血酸在局部达到的浓度。有时，当少量抗坏血酸服用时，花粉对粘膜表面的剌激将会出现，但常见的粘膜下水肿被阻止发生。
消化道感染的有力治疗，如念株菌、肠贾第虫，和其他有害肠道病原体的感染，可逆转相对氧化态的氧化还原电位和使肠道壁的抗体不被激活。许多时候，如果治疗及时，食物和化学物敏感性将会减轻。然而，存在已久的食物过敏可能更加顽固。虽然如此，大剂量抗坏血酸，如果服用足够量，常增加足够的缓解，使结果更满意。
抗坏血酸和卡氏肺囊虫肺炎（PCP）
PCP是爱滋病病人最常见的突然急性死亡原因。用抗坏血酸和磺胺配合治疗尤其有效。在爱滋病的并发症中，PCP最易被抗坏血酸治疗。PCP对抗坏血酸的敏感性是因为这里正在讨论的原理。
极度乏力、疲倦、不适、消瘦等典型的PCP症状一定是急性诱发性坏血病引起，因为病变对大剂量抗坏血酸的特异性反应的快速性。另外，PCP病人中一个主要问题是对磺胺药的过敏反应的发生率是如此之高，以致最后阻碍其在相当高比率病人的使用。正在试验的药物，PENTAMIDINE，本身引起很多不良反应，被使用的一部分原因是磺胺药过敏反应的高发生率，以及部分病人看来对磺胺药的反应不太好。
临床上，抗坏血酸阻断对磺胺药的过敏反应，可能因为正在此讨论的机制。另外，在治疗PCP中，抗坏血酸看来和磺胺药起协同作用。通常可单独使用抗坏血酸治疗有发生PCP病倾向的病人。抗坏血酸，配合爱滋病治疗方案的其他措施，可预防大多数急性PCP袭击。普通感冒和其他呼吸道疾病，容易发展为PCP的，都可以用抗坏血酸预防和治疗。偶然情况下，如果一种呼吸道病毒性疾病很严重，静脉注射抗坏血酸治疗会被采用。一个急性发作的PCP病人通常以门诊病人治疗。如及早治疗，使用抗坏血酸至肠耐受极限，加上合适的磺胺药，发生对磺胺药过敏反应的可能性非常少。
我认为这种配合如此成功的原因是抗坏血酸预防急性诱发性坏血病，而急性诱发性坏血病的部分病理为：产生激活抗体的系统性相对氧化态的氧化还原电位，当抗坏血酸足量使用时，抗体的激活局限在原发病的始发病灶周围的最合理的小范围。增大过敏反应可能性的抗体的广泛激活被大部分阻止。抗体如果在原发病灶被磺胺药激活，这些抗体在流经皮肤时，处于未激活状态，不能和皮肤发生交叉反应产生皮疹。
B细胞和抗体的形成
抗体由B细胞分泌（15），每个B细胞产生配对抗原的抗体。在辅助性T细胞帮助下，抗原被抗原呈送细胞呈送至B细胞受体有精细的方法。B细胞被激活，进一步分化成分泌抗体的抗体形成细胞。
我认为，如果消化酶功能正常，以及如果皮肤和粘膜完整无缺，不让病原体和其他异物进入体内，不会有许多抗原呈送至B细胞。由于炎症损害这些细胞膜，更多抗原会漏进机体，更多抗体会产生。抗坏血酸会减轻继发炎症反应，减少呈送至B细胞的抗原数量，结果，减少抗体形成的数量。
另外，在相对还原态的氧化还原电位的组织，和抗体一样的B细胞受体在B细胞表面亦被还原，由此，抗体的形成得以减少。
T细胞和它的受体
T细胞受体有和抗体类似的结构。T细胞受体由两条和抗体类似的多肽链组成。一条ALPHA，一条BETA，由一个单一的二硫键连结。（16）我推测，这个二硫键会被还原，以及当存在于相对还原的氧化还原状态的正常组织时，T细胞受体位置会处于未激活状态。当遇到自由基或在一个相对氧化的氧化还原状态，受体位置会变为激活态。这个机制会提供一个类似的抑制，如那些体液免疫一样。它会抑制细胞免疫，视其机制使细胞毒性T细胞变成未激活状态。根据它使辅助性T细胞保持未激活的程度，它亦和未激活抗体和B细胞一同限制体液免疫。
抗坏血酸和进化
Irwin Stone博士指出，大部分动物有合成抗坏血酸的能力。约在6500万年前，高级灵长类动物丧失了合成抗坏血酸的能力。这种不能合成抗坏血酸的能力是因缺少一种肝酶,L-古洛糖内酯氧化酶（GLO）—一种从葡萄糖合成抗坏血酸的第四步骤必须的酶而出现(17)。
Levine推测，在紧急应激情形下，如为生存而战斗，一个有抗坏血酸合成能力的动物每小时利用50克的葡萄糖合成50克的抗坏血酸。这会拉低血糖水平，引起血糖波动，可能会削弱其战斗能力（18）。另外，我会增加一项优点，就是一个不利用葡萄糖合成大量抗坏血酸的一个优势是，它可以在没有食物也不受饥饿的情况下，走得更远。
但，也许更重要的，生活在陆地上的动物，以鼻子寻找他们自己和其他动物的粪便，进食已死去和部分腐烂的食物，需要抗坏血酸自由基清除系统给予的额外解毒保护。这个抗坏血酸系统可能是狗可以埋下一根骨头，让它腐烂几天，然后挖出来进食而没有任何问题的原因。高级灵长动物，生活在树上，废物和死物扔掉至地上，变得相对挑食，加上在树上生活的生物的稀疏，更不必要担心感染性疾病。人类历史亦表明，自人类走出树林，大群聚居在一起，感染性疾病更多地成为一个问题。天花、藿乱、鼠疫、伤寒热、斑疹伤寒等，在广泛地区有规律地流行，杀死大百分比的人口。只因现代卫生方法和医学科学的出现才有死亡率的下降。爱滋病也许是一种因为人类的一些卫生机制的漏动而导致的疾病，因为他们缺乏合成抗坏血酸能力。
不管什么原因，高级灵长动物丧失了合成抗坏血酸的能力。除非有某些可得到的代偿机制，以代替抗坏血酸机制的缺乏，如酶类自由基清除剂、超级过氧化物岐化酶、催化酶、谷胱甘肽等，他们可能不能生存。一个远高于足够生活在树上的复杂的免疫系统，已在陆上动物进化而成。
在数千百万年来，可以合成抗坏血酸的动物，进化过程已调整其免疫系统至最优化水平。而不能合成抗坏血酸的灵长动物，仅6500万年的进化，未完全解决这些动物的一种轻度的超敏性倾向。也许，人类智慧的大脑的结果之一是他可能获得某些抗坏血酸制造的优势，而没有丧失不利用葡萄糖在危机下合成抗坏血酸的优势，以及不丧失代偿性酶类自由基清除剂机制的优势。
应注意到，当一种不能产生自由基的微生物进入宿主，宿主的细胞免疫系统可以直接吞噬这种微生物。如果这种微生物有能力产生足够的自由基或控制细胞免疫机制，那么，体液免疫的抗体就会前来救援，抗体被这些自由基激活。在细胞免疫能完成其任务的组织器官，抗体不需要过度参与。抗坏血酸帮助细胞免疫机制，使抗体过度合成和自身免疫反应的危险更少。（15）
小结
因为Heisenberg 不确定法则（Heisenberg Uncertainty Principle），我认为这些推测很难验证，即使受最轻微的干扰，组织都不再正常和健康。虽然如此，出现在此的推测会解释一些关于免疫系统的临床观察报告。尤其是，这些推测会解释我的一些大剂量抗坏血酸对过敏性病变的作用的观察报告。
我推测，一个相对还原的氧化还原状态正常存在于健康组织，以及在某些情况下，抗体的长链和短链之间的二硫键会被还原为巯基。这种状态下，抗体处于未激活状态，不能和抗原配对。这个情形适用于，不管免疫球蛋白存在于血管内或外，粘液、B淋巴细胞的表面、嗜碱性粒细胞和肥大细胞。我推测，一种类似的情形存在于细胞受体位置上。当抗体进入存在自由基或处于氧化态的氧化还原电位的器官组织，抗体被激活，并寻求抗原配对。这种机制限制抗体和自身分子发生交叉反应的范围和时间，因此，减少自身免疫反应的可能性。可这样推测，实际上，某些病理情况控制了机体的自由基清除机制，引起这种超敏感状态出现。大剂量抗坏血酸可以恢复还原态的氧化还原电位，并广泛地解除抗体的武装，把抗体的抗原配对局限于疾病的原始病灶。抗坏血酸合成动物本能地这样生存。
这种机制提供了一个有效的方法，使广泛性的继发炎症连串反应得以预防，因外伤、外科手术、过敏、肿瘤和感染的发病率得以减少。
擦掉牙齿的抗坏血酸和碳酸盐抗坏血酸，因为牙齿长时间接触抗坏血酸会损伤牙釉质。如果大剂量抗坏血酸已服用一段时间，不能突然停药，尤其在紧急情况下。
Submitted to Medical Hypotheses February 13, 1986.
I previously described that bowel tolerance (the amount that almost causes diarrhea) to oral ascorbic acid, increases in a person somewhat proportionally to the "toxicity" of his disease. Ascorbic acid ameliorates symptoms and sometimes cures certain diseases at high threshold levels near bowel tolerance. High concentrations of ascorbate cause the redox potential of the redox couple (ascorbate/dehydroascorbate, AA/DHA) to become reducing in diseased tissues. Allergic and sensitivity reactions are frequently ameliorated and sometimes completely blocked by massive doses of ascorbate. I now hypothesize that one mechanism in blocking of allergic symptoms is the reducing of the disulfide bonds between the chains in antibody molecules making their bonding antigen impossible. I further hypothesize that antibodies seek to match antigens only in areas where stray free radicals or a relatively oxidizing redox potential exists. The redox state of normal, healthy tissue does not allow for the bonding of antibodies to antigen. When antioxidant, free radical scavenging systems are overwhelmed, inflammatory, hypersensitivity, and "autoimmune" conditions may result.
Based on my experience with over 12,000 patients during the past 15 years, it has been my consistent observation that the amount of ascorbic acid dissolved in water which a patient, tolerant to ascorbic acid, can ingest orally without producing diarrhea, increases considerably somewhat proportionately with the "toxicity" of his illness (1,2). A person who can tolerate orally 10 to 15 grams of ascorbic acid in divided doses per 24 hours when well, might be able to tolerate 30 to 60 grams per 24 hours if he has a mild cold, 100 grams with a severe cold, 150 grams with influenza, and 200 grams per 24 hours with mononucleosis or viral pneumonia. Patients with hay fever, asthma, or environmental, drug, and food allergies and sensitivities usually tolerate from between 15 to 50 grams per 24 hours divided in 4 to 12 doses. Occasionally, tolerance is elevated even to higher amounts. There is frequently a dramatic decrease in symptoms just before diarrhea is produced. The individual patient has to be tolerant to oral ascorbic acid to achieve this effect but fully 80% of patients are tolerant enough. I call the process whereby the patient determines an appropriate dose of ascorbic acid, titrating_to_bowel_tolerance. Intravenous sodium ascorbate is even more effective.
I had previously hypothesized (3,4) that this ameliorating effect is largely due to the antioxidant, free radical scavenging effect of massive doses of ascorbate. Additionally, I had hypothesized that oxidants and free radicals formed in pathologic processes, oxidize ascorbate in the diseased tissues, exhausting the ascorbate first in the involved tissues, and then in the body more generally. There is then no vitamin C left over for known vitamin C functions first in the involved tissues, and then in the body more generally. I call this phenomenon acute_induced_scurvy. To the extent that free radicals are formed in allergic and sensitivity reactions, I think that these mechanisms apply. I have much clinical evidence that massive doses of ascorbate will ameliorate the secondary inflammatory cascades of injury and surgery.
I had hypothesized that the threshold where high doses of ascorbate suddenly became effective was where the ascor- bate/dehydroascorbate (AA/DHA) redox couple became reducing in the affected tissues (5). The dehydroascorbate formed, as ascorbate reduces free radicals and oxidizing substances, is not as toxic as the substances it reduced because the oxidizing redox potential of the dehydroascorbate is not as great as the oxidizing redox potential of the free radicals and oxidizing substances reduced. But additionally, if the amount of ascorbate ingested is enough to cause the AA/DHA redox couple to become reducing in the affected tissues, the dehydroascorbate formed will not be at all toxic. We should not just think of the ascorbate being a reducing substance and the dehydroascorbate being an oxidizing substance but should think of the redox potential of the redox couple, ascorbate/dehydroascorbate. I am able to negate any oxidizing effect of dehydroascorbate formed by making sure that the patient always ingests or is administered enough ascorbate to drive ascorbate into the depths of the diseased tissues in concentrations that exceed the dehydroascorbate formed. The redox potential of the redox couple is made reducing in the depths of the diseased tissues.
I have found that ascorbic acid in bowel tolerance doses is able to block many allergic reactions. I was alerted to this possibility when my own seasonal hay fever symptoms were blocked with 16 grams of ascorbic acid orally per 24 hours under conditions of moderate exposure to pollen. However, with exposure to higher doses of pollen, it required increased doses to maintain reasonable blockage of symptoms. Acute exposure to antigens could increased tolerance to 50 grams or more per 24 hours. When the exposure to allergens was very great, the blockage of symptoms was frequently incomplete. Experience with at least 1000 allergic patients has verified this finding in most cases. The limiting factor frequently seems to be the ability of the individual patient to consistently take that amount which almost causes diarrhea. The combination of ascorbate treatments with other treatments may result in even more optimum results.
Asthma attacks are frequently ameliorated similarly. When asthma is induced by exercise, massive doses taken before, during, and after the exercise will usually prevent otherwise expected attacks. Asthmatic attacks provoked by infections, especially upper respiratory infections, are most frequently prevented. The efficacy in these cases is mostly dependent upon the ability of the patient to tolerate sufficient doses of ascorbate. In severe acute situations, intravenous ascorbate may be especially effective in patients unable to take adequate amounts orally.
Urticaria, bee stings, poison oak, eczema, etc. can be ameliorated to varying degrees depending upon the tolerance of the patient to ascorbate and upon other as yet undefined variables. Ascorbate frequently works synergistically with other treatments for these allergic conditions.
Three patients with scarlet fever were treated who had the typical sandpaper like rash. The rash in these cases, the fever, and all other manifestations of the disease vanished in a few hours when the patients ingested bowel tolerance doses of ascorbic acid. The effect of ascorbate on scarlet fever and some food poisonings is so dramatic as to suggest a destruction of a finite amount of toxin which is not being replenished by the disease process.
About 2,000 patients were treated with penicillin, ampicillin, and cephalosporins in conjunction with bowel tolerance doses of ascorbate without any immediate allergic reactions to those medications. There was one delayed serum sickness-like reaction to penicillin in a young child. Her symptoms were temporarily lessened with large doses of ascorbate. It was most likely that she had not taken amounts of ascorbate sufficient to obtain the blocking effects being described here.
Several mononucleosis patients were inadvertently given penicillin along with ascorbic acid and had no allergic reactions. This experience is of note because of the very high incidence of allergic reactions to penicillin in patients with mononucleosis. One patient (having been given penicillin without ascorbate elsewhere) who presented with a typical allergic rash, had the rash disappear in minutes when given ascorbate intravenously.
As the protection of ascorbic acid against allergic reactions to certain antibiotics became increasingly more apparent, I expanded my indications for antibiotics somewhat. While the treatment of established Candida infections with ascorbate is complicated and of value only in conjunction with other treatments, women who have a tendency to vaginal yeast infections whenever given antibiotics, have a marked reduction of this complication when taking bowel tolerance doses of ascorbic acid along with the antibiotics. Additionally, ascorbate seems to act synergistically with antibiotics and significantly broaden the spectrum of activity of the antibiotics.
I have not as yet had a patient have an anaphylactic reaction to anything while taking large doses of ascorbate. The number of possibilities of anaphylactic reactions may have been so few as to make this observation of limited value. However, the spectrum of conditions which ascorbate ameliorates suggests that ascorbate should be taken along with any other indicated treatments whenever there is any danger of anaphylactic reaction.
The observation of Kalokerinos (6) that ascorbate prevents sudden infant death syndrome (SIDS) may or may not be relevant here but bears repeating whenever possible.
While vitamin C has been described as having an anti-histamine like effect (7,8), it is not strictly an antihistamine. Most antihistamines have an ethylamine moiety as is present in histamine but not ascorbate. Antihistamines appear to act by occupying "receptor sites" on effector cells and exclude the histamine; they are pharmacological antagonists. Vitamin C has no real stimulating effect on the central nervous system, as do most antihistamines at certain doses. The relief by ascorbate of malaise and some toxic effects on the brain and body in general, may be interpreted by a patient as somewhat stimulating however. Certainly ascorbate has no depressant effect on the CNS as do antihistamines. Vitamin C has no local anesthetic effect nor an atropine-like effect found with antihistamines. Ascorbate has no acute poisoning effect on the CNS no matter what dose is taken orally as do antihistamines.
Lewin described mechanisms whereby ascorbate assists in the formation of cyclic AMP (9) and cyclic AMP inhibits the release of histamine (10,11) from mast cells or basophils, but this is not an effect of antihistamines.
Therefore, ascorbate may be found to have some of the beneficial clinical effects which in a few instances might be similar to antihistamines, but ascorbate would often ameliorate a condition where an antihistamine had not helped. Additionally, ascorbate seems at times to work synergistically with antihistamines. Ascorbate is certainly not to be considered an antihistamine and has no similar pharmacological mechanism of action.
Food allergies, as those which produce classical IgE mediated symptoms such as urticarial rashes often respond rapidly. Bowel tolerance doses to the extent that they produce softened stools, even diarrhea, and decreased bowel transit time, reduce the duration of the reactions in addition to the blockage of the reactions.
Food sensitivities, or reactions not mediated by IgE frequently present more difficulties but bowel tolerance doses should be tried. Depending upon the underlying cause, one can expect in a significant percentage of patients that the intensity of reactions will be reduced and the duration of the reactions lessened.
Food poisoning and gastroenteritis may be dramatically relieved by massive doses of ascorbate. Experience is helpful in treating these conditions because the patients fear that ascorbic acid will intensify the diarrhea and other bowel discomfort. In an otherwise healthy bowel there is little difficulty. Doses of ascorbic acid far in excess of what would ordinarily be tolerated are administered. These doses do not usually add to the diarrhea but subtract from it. If one inadvertently overdoses greatly on the ascorbic acid, diarrhea will be produced, but there is relief of all of the other toxic symptoms and the diarrhea is benign, not usually associated with any pain.
While it is not always successful, I always test the effect of ascorbic acid on the food or chemical allergic patient. Bowel tolerance doses of ascorbic acid frequently have an ameliorating effect. However, the taking of the necessary doses of ascorbate is frequently difficult because of common nuisance problems in these patients. The production of much intestinal gas is frequent. Many patients with these allergies have a bowel flora that contains Candida albicans (12,13) and other gas producing organisms. Clinically, the sometimes enormous production of gas is suggestive that Candida and other organisms actually ferment ascorbate, or that ascorbate somehow accelerates their fermentation of other foods. However, some patients seem to break through a barrier where even larger doses of ascorbate reduce the amount of gas produced. Perhaps the decreased transit time associated with these large doses of ascorbic acid physically wash out much of the gas producing flora, or perhaps high enough levels of ascorbate finally inhibit fermentation. Interestingly, large amounts of intravenous sodium ascorbate in the range of 60 grams a day for a day or two, administered while the patient takes as much ascorbic acid as possible orally, may "prime" the patient in such a way that large doses of ascorbic acid are well tolerated by mouth. Measures to starve and kill intestinal Candida should be taken and when effective will reduce the intestinal gas.
Some of these patients will be allergic to certain vitamin C preparations. I find that by using the synthetic ascorbic acid fine crystals derived from corn syrup, the incidence of these reactions is reduced. Nevertheless, allergic symptoms will sometimes occur. Experience has shown that it is not the ascorbate itself which causes the allergic reaction but that some trace contaminant introduced in the manufacturing processes is responsible. When difficulties are encountered, other forms of ascorbate should be tried. Ascorbic acid made from sego palm, certain preparations labelled "natural", sometimes tablets or even timed-release forms may be better tolerated by individual patients. But these forms are more expensive and if used initially, may even more likely cause reactions. The most serious problem with certain alternative forms of ascorbic acid is that they may not have as beneficial an effect because blood levels of ascorbate reached are frequently not as high.
If mineral ascorbates are used, be mindful of the fact that it is the ascorbate part which is being discussed here and that the amount of mineral taken should be considered. Mineral ascorbates alter bowel tolerance in ways which have nothing to do with the mechanisms being discussed here. Calcium, magnesium, and potassium salts are sometimes used by allergic patients to block certain reactions and, when effective in an individual patient, may as well be used in the ascorbate form. This introduces a subject beyond the scope of this paper.
While it is not always successful, it is worth the effort to have every food allergic patient try to take bowel tolerance doses of ascorbic acid. If the bowel can tolerate it, tolerance doses may ameliorate symptoms of food and chemical allergy to varying degrees.
The definite effect of ascorbate on IgE mediated and other immunoglobulin mediated allergies has suggested to me a possible mode of action which can be understood in specific biochemical terms.
Although there are five distinct classes of human immunoglobulins, IgG, IgA, IgM, IgD, and IgE antibodies, the basic unit of immunoglobulin structure consists of two identical light polypeptide chains and two identical heavy polypeptide chains linked together by disulfide (SS) bonds. The classic model of this basic unit has these chains arranged in a "Y" shape. The two heavy chains have an angle (called the hinge) toward their middle and are linked together by SS bonds in such a way as to form together the base of the "Y". This base, or Fc fragment, mediates the binding of the antibody to host tissues, including various cells of the immune system, some phagocytic cells, and compliment. The SS bond linking in the base of the "Y" differs in different classes and even different subclasses of immunoglobulins. In the case of IgM, five of the basic units are joined together at their bases.
Each of the two light chains link to either side of the "V" of the "Y" shaped arrangement of the heavy chains, each by way of a single SS bond. Each of the two sides of the "V", made up of about half of a heavy chain and the whole of a light chain and bound together by the SS bond, are named Fab fragments. The upper ends of these Fab fragments are the specific antigen binding sites and are where antigens are bound.
Although the following analogy involves some inaccuracies, think of each Fab fragment of the "V" as being like a clothespin, the two wooden parts (part of one heavy chain and all of one light chain) being held together by a spring. The spring represents the SS bond. The far end of the wooden parts are called variable domains and are variously shaped so that they fit different antigens. When the pair of "clothespins" of an antibody find a match with an antigen, they hold onto that antigen.
In the IgE molecule there are 20 SS bonds. Sixteen are intrachain bonds. Two interchain SS bonds link the two heavy chains in the hinge region of the upper end of the Fc portion. One interchain SS bond links each of the two light chains to the adjacent heavy chains near the hinge. In vitro, by consecutive increases in the concentration of such reducing agents as dithiothreitol (DTT) and alkylation, one can sequentially disrupt the SS bonds (14). With a DTT concentration of 1 mM, the interchain SS bonds between the heavy and light chains are disrupted. These bonds are in the variable regions that bind antigen. Like taking the spring out of the clothespin, the antibody becomes unable to bind antigen. At a concentration of 2 mM of DTT, the SS bond within the heavy chains near the hinge are reduced and there is a marked decrease in the ability to attach to target cells (basophils and mast cells in the case of IgE). Higher concentrations of DTT cause more reduction and disruption of the IgE antibody.
Lewin (9), has analyzed biochemically the complex conditions favoring the reduction of disulfides by ascorbate in the human body. He concludes that under the conditions which exist in the human body, the ascorbate/dehydro- ascorbate system can reduce the thiol/disulfide system (i.e., ascorbate is capable of reducing SS bonds) when ascorbate is well supplied. Although Lewin did not specifically mention the SS bonds of antibodies, he did mention the dithiothreitol (DTT) (utilized in the experiment above), cystine, glutathione, and adrenochrome among others.
Symbolically, the reactions may be represented:
AA = DHA + 2e + 2H+
-S-S- + 2H+ + 2e = 2-SH
One gains the impression from Lewin's analyses of several metabolic systems in the human body, that it is very possible that certain systems are in an equilibrium such that if the concentration of ascorbate to dehydroascorbate is high, the system will be reduced and usually favorably influenced. My clinical experiences have verified these impressions. I would differ with Lewin only in that I have found the magnitude of the doses necessary clinically to accomplish these feats are 10 to 15 times what he anticipated in serious disease states.
Clinically, allergic reactions are blocked by ascorbate somewhat to the degree that a threshold concentration of ascorbate might be being pushed into the affected tissues. The amount of ascorbate required seems somewhat proportional to the inflammation in the affected tissues. The threshold amount could be the amount of ascorbate necessary to reduce the free radicals and other oxidants present in the inflamed tissues, establish a relatively reducing redox potential in those tissues, and reduce the SS bonds of the antigen binding ends of the antibodies.
I hypothesize that an important effect of normal levels of vitamin C and other antioxidants is to reduce each of the interchain SS bonds of the two antigen binding ends of the antibody. The antigen binding ends are altered in such a way as they cannot bind anything. The pieces do not fly off in every direction but are held together, probably by Van der Waals forces, but still cannot bind anything.
Additionally, I hypothesize that this "unprimed" state is the usual state of antibodies in normal, healthy tissues. Antibodies are not "primed" to match antigens unless the antibodies wander into areas that have many free radicals or a relatively oxidized redox state. The problem in humans is that with surgery, injury, infection, allergic reaction, etc., the redox potential of affected tissues, because of free radicals and oxidants and the inability to make ascorbate, becomes less reducing too easily and antibodies become primed over an unnecessarily wide area and for too long a duration of time.
At first this unpriming effect might seem very undesirable under certain conditions but I think that ascorbate assists the body in modulating the antibody response toward an optimum. Certainly, the antibody response in hay fever, asthma, urticarial rashes, etc. does no good and that ascorbate should block these is desirable. An ideal situation would be that pollen, lying harmlessly on mucous membranes, would not be bound by antibodies because the antibodies would be unprimed, but that a bacteria or virus, etc. putting out toxins to ward off the immune system, would prime antibodies and cause antibodies to start seeking a match.
In my limited experience with ascorbate producing animals, I have noticed that in the cases of their surgery, injury, and infection, there is seemingly a shorter period of pain and disability than with humans. It is as if there were not the degree of secondary inflammatory cascade which is experienced by humans. This impression was verified by veterinarians. It was my impression dealing with many human injuries in a ski resort area that while acute pain immediately following an injury or surgery is not reduced, the pain the next day is reduced considerably when the patient is saturated with ascorbate. When an injury is totally immobilized or is not disturbed, it is common for there to be almost no pain at all in 24 hours. The lack of secondary inflammation is striking.
My experience with avulsed pieces of skin has been that when the piece was properly reapplied surgically, that if at the time of reimplantation the piece was viable, it would almost invariably survive. The dying of autogenous grafts caused by circulation being impaired due to secondary inflammation was virtually eliminated when large doses of ascorbate were taken.
In the case of infections, inflammation seems less in amount and duration in patients taking bowel tolerance doses of ascorbic acid. The inflammation seems more confined to the limited area directly involved in the infection. Nevertheless, most infections are shortened or aborted by ascorbate, seemingly by mechanisms mostly unrelated to inflammation. The theoretical value of reducing inflammation in treating many infections is attested to by the fact that physicians sometimes use steroids when treating infections, despite the fact that steroids seem to inhibit certain infection fighting mechanisms. In contrast, adequate doses of ascorbate seem to block inflammation to a more optimum degree while augmenting various infection fighting mechanisms.
I think that ascorbate, at the dose levels being discussed, manages to reduce the interchain SS bonds of antibodies except directly down on the tissues directly infected where the free radicals and oxidants are intensely concentrated. In the depths of infection, ascorbate assists the phagocytes maintain the respiratory burst killing of pathogens while protecting adjacent tissues from stray free radical damage (5).
Secondary inflammatory cascades are shut down by high doses of ascorbate scavenging free radicals, thereby preventing an unnecessarily wide area of relatively oxidized redox potential. Antibodies therefore remain unprimed, except in the small area most intensely directly affected by the injury or infection. The antibodies are prevented from unnecessarily matching antigens in what would have otherwise been large areas of secondary inflammation. Therefore the tendency toward autoimmune reactions is cut down considerably.
My hypothesis does not in anyway negate any of the elegant mechanisms of immunoregulation which have been worked out to explain necessary controls of the immune response but it adds a very effective control mechanism which markedly limits the area in which the more complex mechanisms must act.
Clinically, it is not uncommon to have a patient complain that an area of an old injury or old infection becomes symptomatic when he becomes ill subsequently with some other condition. Antibodies, formed by matching slightly altered self-molecules, slightly altered by the previous injury or infection, were at the time of the original insult suppressed as the original inflammation resolved. There have been described multiple mechanisms of immunoregulation in immunology texts whereby antibody reactions are brought under control (15). I hypothesize that an additional mechanism of suppression is that as the normal relatively reduced redox potential of the tissues is restored, the antibodies become reduced and unprimed. Subsequently, when the patient's free radical scavenging mechanisms are overwhelmed by some different condition, the redox potential in the body systemically becomes more oxidizing and old antibodies begin to seek matches. Some antibodies generated during the previous insult may then match those previously affected areas and result in pain and inflammation. Additionally, those antibodies may cross react with tissues similar to the previously affected tissues and more generalized conditions such as arthritis, myositis, tendonitis, neuritis, etc. may result. Foreign body molecules, especially from foods and chemicals, similarly may multiply antibodies which cross react with self-molecules. Ascorbate is frequently extremely effective in averting this situation because the systemic redox potential is kept relatively reducing despite local pathological processes generating considerable quantities of free radicals.
Sometimes fully developed autoimmune reactions can be markedly ameliorated by massive doses of ascorbate by driving reducing redox potentials directly into the depths of the autoimmune reactions. Quite frequently, if high levels of ascorbate are maintained such that the autoimmune response is mostly but not completely blocked, the reaction may become intermittent and reveal itself to be related to some previously unsuspected antigen and not be a true autoimmune reaction after all. In patients suspected of having food and chemical sensitivities, it may be difficult to determine by history which foods and chemicals are causing reactions because the reactions last for days. Frequently, the duration of these reactions are shortened by large doses of ascorbate sufficiently that the cause of the reactions become more obvious.
It is not uncommon to have a patient confused as to whether he is allergic to a certain substance or not because sometimes he seems to react to it and sometimes not. If, for instance, the patient has antibodies to certain milk proteins but he is otherwise under no stress, there are no inflammations going on, and the free radical scavengers of the body have a relatively reducing redox potential established in all tissues, then the patient will be able to drink some milk because all the antibodies will be in an unprimed state. But, if the free radical scavenging mechanisms have been overwhelmed systemically or locally in the gut exposed to the milk, the antibodies will be primed and will react if exposed to the milk antigen.
Free radical scavengers can be exhausted systemically by free radicals resulting from exposure to chemicals such as formaldehyde, chronic infections such as Epstein-Barr viral infections, other allergic reactions, injury, emotional stress, etc. resulting in priming of antibodies systemically. The more antibodies primed systemically, the more likely cross reactions will occur with self-molecules and autoimmune reactions occur.
Local reactions may exhaust free radical scavengers locally and prime antibodies. Particularly bothersome in this manner is Candida which is able to prime antibodies in the gut and lead to sensitivity reactions to the Candida itself and to many of the foods currently being eaten. Amoeba, Giardia and other intestinal pathogens may act similarly. As the inflammatory reactions become more intense and more free radicals are released, establishing more oxidizing redox potentials over wider areas, more antibodies are primed and sensitivities become more severe and more numerous. Inflamed mucous membranes are not as able to make appropriate digestive enzymes and therefore more macromolecules (e,g. undigested whole food proteins) would gain entrance into the body and be more likely to cause the production of matching antibodies.
Diseased mucous membranes and skin are more likely to admit antigens of all sorts including improperly digested macromolecules. Poor diet or overutilization of certain nutrients caused by stress, can result in digestive enzyme deficiencies from lack of nutrients necessary to make those enzymes. Poor diet and stress can also result in insufficient free radical scavengers to keep the redox potential sufficiently reduced to unprime antibodies. Junk foods can cause a patient to become allergic to good foods. Clinically. I have seen sugar ingestion cause hay fever attacks to pollen.
On the other hand, relief of exposure to antigen may allow the body to quiet inflammatory reactions, temporarily catch up with free radical scavenging, and allow for a temporary tolerance to an antigen because the antibodies are unprimed. For instance, a person with hay fever may, if put into an environment completely free of pollen for a period of time, subsequently be able to tolerate a moderate amount of pollen without immediately reacting because the antibodies in the nose had become unprimed. As a topical mild irritation starts in the nasal mucosa, a more oxidative redox potential is set up, the antibodies prime over a wider area and a more severe allergic reaction ensues. High doses of ascorbate can keep the area reduced to a greater degree and allow tolerance to higher exposure to pollen depending upon the concentration of ascorbate achieved in the mucous membranes. Sometimes when moderate doses of ascorbate are taken, there will be superficial irritations in the mucous membranes from pollen but the usual deep edema is averted.
Vigorous treatment of infections of the gut, such as Candida, Giardia, and other unfavorable intestinal pathogens, may reverse the relatively oxidizing redox potential and unprime the antibodies in the gut wall. Many times food and chemical sensitivities will be relieved if treatment is early enough. However, food sensitivities present for long periods may be more fixed. Nevertheless, massive doses of ascorbate, if taken in sufficient amounts, frequently add enough relief to make the result more satisfactory.
Pneumocystis carinii pneumonia (PCP), the most common immediate cause of death in AIDS patients, is particularly effectively treated with a combination of ascorbate and sulfa drugs. Of the complications of AIDS, PCP is the most easily treated with ascorbate. The responsiveness of PCP is because of the principles being discussed here.
The profound debility, fatigue, malaise, weight loss, etc., typical of PCP must be from acute induced scurvy because of the rapidity with which the condition responds specifically to ascorbate taken in high doses. Additional- ly, a major problem in PCP patients is that the incidence of allergic reactions to the indicated sulfa drugs is so high as to ultimately prevent their use in a high percentage of patients. The experimental drug, pentamidine, which causes many unfavorable reactions itself, is used partly as a result of this high incidence of allergic reaction to sulfa drugs and partly because some PCP cases seem not to respond favorably to the sulfa drugs.
Clinically, ascorbate blocks the allergic reactions to the sulfa drugs probably because of the mechanisms being discussed here. Additionally, ascorbate seems to works synergistically with sulfa drugs in the treatment of PCP. Usually it is possible to treat the patient who has a tendency toward PCP with ascorbate alone. Ascorbate, in combination with the rest of the AIDS protocol (3,4), will prevent the majority of attacks of acute PCP. The common cold and other respiratory diseases which predispose to the development of PCP can usually be prevented or treated with ascorbate. Occasionally, treatment with intravenous ascorbate is indicated if a respiratory viral disease is very severe. A patient with an actual attack of PCP can usually be treated as an outpatient, if caught early, with bowel tolerance doses of ascorbate plus the appropriate sulfa drug without difficulty and with very little probability of allergic reaction to the sulfa drug.
I think that the reason this combination is so successful is that the ascorbate prevents the acute induced scurvy, part of which is the creation of a relatively oxidative redox potential systemically which primes the antibodies. When ascorbate is used in adequate doses the priming of the antibodies is confined to an optimum small area directly about the primary site of the disease. The widespread priming of antibodies which increases enormously the probability of allergic reactions is mostly averted. If antibodies are formed to the sulfa drug in the primary site of the disease, those antibodies are in a unprimed state when circulating through the skin and cannot cross react with the skin and cause a skin rash.
Antibodies are secreted by the B cells (15). Each B cell produces antibodies which match a single antigen. There are elaborate methods whereby antigen is presented to the B-cell receptors by antigen-presenting cells with the help of T-helper cells. The B cells are stimulated to differentiate and divide into antibody forming cells which secrete the antibodies.
I think that if all the digestive enzymes are functioning properly and if the skin and mucous membranes are intact not allowing pathogens and other foreign macromolecules inside the body, not much antigen will be presented to the B cells. With inflammation damaging those membranes, more antigens will leak into the body and more antibodies will be produced. Ascorbate would lessen the area of secondary inflammation and thereby reduce the amount of antigen presented to the B cells and therefore reduce the amount of antibodies formed.
Additionally, it may be that the B-cell receptors (being identical to the antibodies) on the surface of the B cells are also reduced in tissues with relatively reduced redox potential and the formation of antibodies lessened for that reason.
T cell receptors have a structure similar to antibodies. The T cell receptor is made up of two polypetide chains, an alpha chain and a beta chain, which are, similarly to the antibodies, joined by a single disulfide bond (16). I hypothesize that this SS bond will be reduced and the T cell receptor site will be in an unprimed state when existing in normal tissues where there is a relatively reduced redox state. The receptor site would become primed when encountering free radicals or an area of relatively oxidized redox state. This mechanism would provide a similar restraint on cellular immunity cross reactions as with those of humoral immunity. To the extent this mechanisms unprimed cytotoxic T cells, it would restrict cellular immunity. To the extent it unprimed helper T cells, it would also (along with unpriming antibodies and B cells) limit humoral immunity.
The late Dr. Irwin Stone pointed out that most animals have the ability to make ascorbate. The higher primates lost the ability to make ascorbate about 65 million years ago. This inability to make ascorbate came about because of the loss of the liver enzyme l-gulonolactone oxidase which is necessary for the last step in making ascorbate from glucose (17).
Levine speculated that in emergency stress such as fighting for its life, an ascorbate making animal might utilize over 50 grams of glucose per hour in order to make 50 grams of ascorbate. This drain on blood glucose levels and resulting fluctuating levels of blood sugar, might impair its ability to fight (18). Additionally, I would add that there is an advantage to an animal in not utilizing glucose for the production of large amounts of ascorbate in that it could go longer without food without starvation.
But, perhaps more importantly, animals living on the ground who nose around in their own and other animals' wastes and eat dead and partially rotting foods, need the extra protection of detoxification afforded by the ascorbate free radical scavenging system. This ascorbate system is probably the reason a dog can bury a bone and let it rot for a few days and then dig it up and eat it without any difficulties. Up in the trees, wastes and dead things drop to the ground. The higher primates probably became relatively picky about what they ate, and living in sparse populations in the trees, had less to worry about from infectious diseases. The history of mankind indicates that as humans came out of the trees and lived together in large groups that infectious disease became more of a problem. Smallpox, cholera, plague, typhoid fever, typhus, etc. would regularly kill large percentages of the population of humans in large areas. Only with the advent of modern sanitation and medical science has there been a decrease in the deaths. AIDS is perhaps a disease which results from laxity of certain sanitation principles necessary in humans because of their lack of ability to make ascorbate.
Whatever the reason, higher primates lost their ability to make ascorbate. They probably could not have survived unless there had been some compensatory mechanisms available to make up for the lack of the ascorbate mechanism such as the enzymatic free radical scavengers, superoxide dismutase, catalase, glutathione, etc. A very complex immune system had been evolved in mammals who lived on the ground which was more than adequate for survival in the trees.
The evolutionary process fine tuned the immune system for hundreds of millions of years in animals who were able to make ascorbate. The mere 65 million years of evolution of the nonascorbate making primates has not completely solved a moderate hypersensitivity tendency in those primates. Perhaps one of the results of the big brain of homo sapiens will be that he will be able to acquire some of the advantages of the ascorbate making mechanisms without losing the advantage of not utilizing glucose for making ascorbate in a crisis and also not losing the advantages of the compensatory enzymatic free radical scavenging mechanisms.
It should be noted that when an organism which is not able to produce free radicals enters a host, the host's cellular immune systems can directly phagocytize that organism. If the organism has the ability to make enough free radicals to suppress cellular immune mechanisms, then antibodies of humoral immunity come to the rescue. Where cellular immunity is suppressed by free radicals, the antibodies are primed by those same free radicals. Where cellular immunity can accomplish its assigned task, antibodies need not become overly involved. Ascorbate assists cellular immune mechanisms and makes less likely the overproduction of antibodies and the risk of autoimmune reactions.
I suspect that these hypotheses will be difficult to prove because of the Heisenberg Uncertainty Principle. Even with the slightest disturbance, tissues are no longer normal and healthy. Nevertheless, such hypotheses as presented here would explain some clinical observations about the immune system. Particularly, these hypotheses would explain some of my observations of the actions of large doses of ascorbate in allergic conditions.
I hypothesize that a relatively reduced redox state normally exists in healthy tissues and that the disulfide bonds between the long and short chains of antibodies are reduced to thiols under these circumstances. The antibodies in this state are unprimed and unable to match antigens. This situation would apply whether the immunoglobulin existed in intra or extravascular pools, mucous secretions, on the surface membranes of B lymphocytes, basophils or mast cells. I hypothesize that a similar situation exists with T cell receptor sites. When the antibodies come into areas of the body where free radicals or an oxidizing redox potential exist, the antibody becomes primed and seeks antigen matches. This mechanism limits the area and time where antibodies may cross react with self-molecules and therefore reduces the probability of autoimmune disease. It is hypothesized that where this mechanism fails, a state of hypersensitization comes to exist despite other immunoregu- latory mechanisms. It is hypothesized that in fact, certain pathological conditions overwhelm free radical scavenging mechanisms in the human body and cause this state of hypersensitization to come to exist. Large doses of ascorbate can restore the relatively reduced redox state and disarm the antibodies systemically limiting the antigen seeking of antibodies to the primary areas of disease. Ascorbate producing animals do this naturally.
This mechanism provides an effective means where widespread secondary inflammatory cascades can be prevented. The morbidity from injury, surgery, allergy, tumors, and infection is reduced.
Rinse ascorbic acid and carbonated ascorbates off the teeth as prolonged exposure may cause damage to the enamel. Do not stop large doses of ascorbate suddenly when large doses have been taken for some time; especially do not stop it in a crisis situation.
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Content (C) 1995 and prior years, Robert F. Cathcart MD.